Following the top-line data announcement in February 2022 that Illuminate, ProQR’s pivotal Phase 2/3 trial of sepofarsen in CEP290-mediated Leber congenital amaurosis 10, or LCA10, did not meet the primary endpoint of Best Corrected Visual Acuity (BCVA) at month 12 compared to a sham procedure control group, comprehensive post-hoc analyses of the trial and trial conduct were undertaken which revealed:
- No technical errors in the trial conduct, data handling, or the medicine product used.
- The overall safety profile of sepofarsen was consistent with earlier trials.
- When the effect in the sepofarsen treated, eye was compared to the untreated eye in the same patient, at month 12, a benefit in vision was observed. This effect was not observed in the control group that received a sham treatment.
- Other endpoints showed similar effect when comparing treatment to contralateral eye, including Full Field Stimulus Testing (FST).
- These findings were supported by the patient reported outcomes analysis, based on the Patient Global Impressions-Change (PGI-C) that demonstrated that 61% of patients in the treatment groups reported an improvement in vision, as well as by Visual Function Questionnaire 25 (VFQ-25).
Overall, the post-hoc analyses showed that the efficacy signal seen with sepofarsen when comparing the active treatment and sham eyes to their corresponding contralateral eyes across BCVA, FST, and other endpoints, including PROs, is more consistent with the results seen in earlier trials, where the contralateral eye was used as the control.
Based on these results, ProQR will focus on the following core activities related to sepofarsen:
- In Q3, ProQR plans to meet with the EMA and FDA to discuss these data from the Illuminate trial. Following this discussion, ProQR will share an update in Q3 or early Q4.
ProQR currently plans to continue Illuminate, which is a 2-year study, the Brighten pediatric study, and the Insight open-label extension study, until further Regulatory guidance, after post which next steps will be determined.